There is a general interest in the design, synthesis and development of hybrid-drugs or multi-target drugs which can increase the probability of the treatment or efficacy by acting on two or more proven pathways of validated targets. For example, cancer cell survival relies on many key pathways, thus, the blockade or inhibition of one pathway may only have a small probability of killing the cancer cells or inhibiting the growth of cancer cells. Cancer cells can compensate or bypass the blocked function or pathway and even synergize their functions. This principle has been validated and is already in use, for example, in combination chemotherapy for cancer treatment, where a combination of drugs such as histone deacetylase (HDAC) inhibitors vorinostat and a variety of known drugs in clinical trials, cocktail drugs for HIV treatment, and augmentin (a mixture of amoxicillin and clavulanic acid) for antibacterial treatment are administered together. There are also successful multi-target drugs in the market, such as multi-kinase inhibitors sunitinib and sorafenib. Both combination therapy and multi-target drugs are aimed to enhance efficacy and/or overcome drug resistance by modulating or inhibiting multiple targets, pathways or networks involved in disease progression. Combination therapy or polytherapy uses more than one drug, thus its advantage is that there are a number of single agents that are available for combination and there are options for testing a variety of combinations of drugs for research and development. However, combination therapy has disadvantages. For example, single agents in general are developed for single agent therapy only and are not necessarily optimized for combination therapy. Further, not all single agents are suitable for or compatible with combination therapy. Defining the dosage regime for two or more agents in combination is a very complex process which requires consideration for dosage level, sequence of administration and potential drug-drug interaction in clinical settings. Further, in addition to the cost of having to use multiple drugs, combination therapy can often lead to unwanted adverse effects or dangerous drug-drug interactions. For example, everolimus was combined with sorafenib in a phase I clinical trials for treatment of advanced hepatocellular carcinoma cancer (HCC), but its dose could not be escalated to a biologically effective concentration due to adverse events.
In contrast, a multi-target drug molecule, as a single agent, works on at least two targets. The advantage of multi-target drugs is that a single agent can achieve modulation of multiple (kinase) targets simultaneously. However, the number of drugs that can do this is still limited. As multi-target drugs typically encompass the chemical features of the scaffolds of both parent drugs, the molecular weight or size of the drug is usually larger, and this often leads to the drug not receiving sufficient exposure either due to toxicity or drug metabolism. It is not a trivial task to design new molecules based on two scaffolds of the parent drugs. Usually the desired efficacy is not obtained or there are new undesired side effects. It is therefore not predictable how to combine two scaffolds to achieve a new multi-target drug. Therefore an observed good activity without undesired side effects is a surprising finding.
There is therefore a need to provide a compound that overcomes, or at least ameliorates, one or more of the disadvantages described above. There is also a need to provide a pharmaceutical composition comprising the compound, methods for treating diseases using the compound and a method for synthesizing the compound.